The present invention relates to a process for preparing an ocular lens with urethane compound and a process for preparing a urethane compound for medical instruments. More particularly, the present invention relates to a process for easily preparing a urethane compound (macromonomer) showing high safety, which is very useful for a material of medical instruments represented by optical materials, for example, an ocular lens such as a contact lens and an intraocular lens, artificial cornea, cornea onlay, cornea inlay. Furthermore, the present invention relates to a process for preparing a urethane compound while molecular weight of the compound is controlled.
At present, various urethane compounds such as urethane foam, urethane rubber, adhesives and polyurethane synthetic fiber are industrially used. Urethane compounds are used for medical instruments such as gloves, various kinds of tubes and catheters, and investigated to be applied for an artificial cornea (Japanese Unexamined Patent Publication No. 325369/2000), an artificial heart, and the like.
In absence of a catalyst or in the presence of a compound such as an organic metal compound or a tertiary amine, hydroxyl group is reacted with isocyanate group to form urethane bond. Particularly, from the viewpoint of high catalytic activity, the organic metal compounds are generally used. Among them, an organic tin compound is well known. For example, an ocular lens is reported which is made of a polyurethane compound prepared by using an organic tin compound as a catalyst (U.S. Pat. No. 4,605,712 and the like).
However, it is considered that the organic tin compound which is generally known as a compound showing high toxicity must not be used as a catalyst for preparation of urethane materials when the urethane materials are applied for medical instruments, such as an ocular lens, which are used in living organism or by contacting with living organism. The organic tin compound is recognized as a distraction substance for endocrine (environmental hormone) which is recently topical substance. Accordingly, some catalysts other than organic tin compounds are earnestly necessitated.
From the viewpoint of mechanical strength and excellent oxygen permeability, urethane compounds containing siloxane structure have been examined for the use as medical instruments, in particular, optical materials such as a contact lens material and an intraocular lens material (Japanese Unexamined Patent Publication No. 22487/1979, Japanese Unexamined Patent Publication No. 121826/1994, U.S. Pat. Nos. 5,451,617, 5,260,000, 5,760,100 and the like). However, because the urethane compounds disclosed in these references are prepared by using the organic tin compounds almost, these urethane compounds are not suitable as medical materials on the basis of the above reasons. Even if purification of the urethane compound is carried out, the organic tin compounds remain within the urethane compound.
Usually, the above urethane compounds containing siloxane structure (macromonomers) have been prepared by finally introducing a polymerizing group in a polyfunctional polysiloxane which is a main chain through urethane bond (Japanese Unexamined Patent Publication No. 179217/1986, Japanese Unexamined Patent Publication No. 35014/1991 and the like). However, when this method is employed, it is inevitable that the polymerizing group is inestimably and repeatedly introduced in the polyfunctional polysiloxane which is a main chain through urethane bond. As a result, molecular weight of the obtained urethane compound becomes higher than planned molecular weight. Accordingly, there is a problem that clear understanding for structure of the obtained compound is difficult.
Because the above urethane compound containing siloxane structure becomes high viscous solution according to its molecular weight or kind of reaction components, effective purification methods for the urethane compound are not developed. So, it is very difficult to remove impurities such as the above catalyst and by-products, and crude urethane compound is used. Accordingly, the use of the urethane compounds has been feared from the viewpoint of safety, including the above problems.
Use of an amine catalyst instead of the organic tin compound for preparing a urethane compound for a medical material is reported (U.S. Pat. No. 4,136,250). However, they are well known generally that specific amine catalysts have cytotoxicity (U.S. Pat. No. 5,955,560), and that amine catalysts are inferior to organic metal compounds in catalytic activity for reaction forming urethane bond and therefore requiring a long time for preparing a urethane compound and increasing a formation ratio of by-products.
Therefore, various organic metal compounds have been investigated as a reaction catalyst for forming urethane bond, because they have a high reaction activity for forming urethane bond, and a low cytotoxicity.
For example, using an acetylacetonate salt of metal such as zinc, iron, or copper is reported for urethane reaction (U.S. Pat. No. 4,879,032, Polymer preprints, Japan, 50, 1258, 2001). However, safety such as cytotoxicity is not evaluated. There are not disclosed effects such as reaction selectivity as a reaction catalyst for forming urethane bond by using a diisocyanate such as bifunctional compound.
When urethane materials are applied for medical materials, for example, medical instruments such as an ocular lens used in a living organism or by contacting with a living organism, remaining of the above mentioned organic metal compound in a formed urethane compound is not preferable even if the cytotoxicity is comparatively low. A method for removing an organic metal compound from a formed urethane compound has not been reported in detail.
Since the above mentioned urethane compound may be formed as a high viscosity solution according to the molecular weight and kinds of reaction substances, there is no effective purifying method. As a result, it is very difficult to remove the above mentioned impurities such as catalysts and by-products, and therefore the urethane compound is used without purification, and there are problems in safety including the above-mentioned problem.
An object of the present invention is to provide a process for easily preparing a urethane compound, in particular, while molecular weight of the compound is controlled, in the presence of a catalyst showing lower toxicity instead of the conventional organic tin compounds and to provide a process for preparing an ocular lens with the urethane compound.
This and other objects of the present invention will become apparent from the description hereinafter.
In accordance with the present invention, there is provided a process for preparing an ocular lens with a urethane compound comprising the steps of
a) preparing a urethane compound by reacting at least one hydroxyl compound and at least one isocyanate compound in the presence of an organic iron compound,
b) removing the organic iron compound from the urethane compound obtained in the step a)
c) mixing the urethane compound obtained in the step b) with at least one compound selected from the group consisting of another copolymerizable compound, a crosslinking agent, a UV absorbent, a dye, a polymerization initiator, a photosensitizer, and an organic solvent to obtain a mixture, and
d) curing the mixture obtained in the step c) to prepare a lens.
In accordance with the present invention, there is also provided a process for preparing a urethane compound for medical instruments, characterized by reacting a hydroxyl compound with an isocyanate compound in the presence of an organic iron compound represented by the formula (I) 
in which each of R1 and R2 is independently selected from the group consisting of methyl group, trifluoromethyl group and phenyl group, as a reaction catalyst to give a urethane compound.
According to the process of the present invention, a urethane compound showing high safety, which is very useful for a material of medical instruments represented by optical materials, such as an ocular lens, can be easily prepared, in particular, while molecular weight of the compound is controlled.